The long range objective of this research is to understand the mechanism of insulin resistance in muscle tissue of diabetics. Muscle is an important tissue to study in diabetes because it is quantitatively the most important tissue in the disposal of glucose, and the postprandial hyperglycemia that is seen in diabetic patients may be due to a defect in the glucose transport system of muscle plasma membranes. However, this hypothesis has not been proven in human diabetics because there has not been a suitable in vitro muscle preparation that could be used to study glucose transport. We have now developed a muscle preparation suitable for such studies and believe that the defects in glucose transport in diabetes can be investigated. Through a cooperative research effort with the Department of Surgery we have a unique opportunity to obtain muscle tissue from a substantial number of morbidly obese patients with noninsulin dependent diabetes mellitus (NIDDM) and we plan to use this tissue to investigate the cause of insulin resistance type II diabetes. Abdominal muscle will be obtained from morbidly obese (normal glucose tolerance, impaired glucose tolerance, and NIDDM) patients undergoing gastric bypass surgery and from nonobese and obese (nondiabetic) patients undergoing elective abdominal surgery. With these tissue samples we plan to: (1) establish that in vitro incubated muscle fiber strips from diabetic patients are resistant to the action insulin, (2) determine the metabolic profile of human muscle in diabetes, (3) study insulin receptor in muscle of diabetic patients, (4) determine the effect of diabetes on the number and distribution of glucose transporters in muscle. Having access to muscle tissue from patients with type II diabetes given us a very unique opportunity to investigate the cause of insulin resistance in muscle. The studies we propose will not only be important for the clinical treatment of diabetes but will also add significant information about the mechanism of insulin action in muscle.